369 research outputs found
Detecting and Explaining Conflicts in Attributed Feature Models
Product configuration systems are often based on a variability model. The
development of a variability model is a time consuming and error-prone process.
Considering the ongoing development of products, the variability model has to
be adapted frequently. These changes often lead to mistakes, such that some
products cannot be derived from the model anymore, that undesired products are
derivable or that there are contradictions in the variability model. In this
paper, we propose an approach to discover and to explain contradictions in
attributed feature models efficiently in order to assist the developer with the
correction of mistakes. We use extended feature models with attributes and
arithmetic constraints, translate them into a constraint satisfaction problem
and explore those for contradictions. When a contradiction is found, the
constraints are searched for a set of contradicting relations by the
QuickXplain algorithm.Comment: In Proceedings FMSPLE 2015, arXiv:1504.0301
Response to combination therapy with interferon alfa-2a and ribavirin in chronic hepatitis C according to a TNF-alpha promoter polymorphism
Background. Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of chronic active hepatitis C. Polymorphisms in the promoter region of the TNF-alpha gene can alter the TNF-alpha expression and modify the host immune response. The present study aimed at the correlation of the G308A TNF-alpha polymorphism with the response to antiviral combination therapy in chronic hepatitis C. Patients and Methods: 62 patients with HCV and 119 healthy unrelated controls were genotyped for the G308A TNF-alpha promoter polymorphism. The patients received 3 x 3 million units of interferon alfa-2a and 1,0001,200 mg ribavirin daily according to their body weight. A response was defined as absence of HCV-RNA and normalization of S-ALT after 6 months of combination therapy. Results:With respect to the allele and genotype frequency, a significant difference was not observed between controls and patients with chronic hepatitis C. Furthermore, such a difference was also not observed if responders and non-responders to antiviral therapy were compared. Conclusions: The promoter polymorphism of the TNF-alpha gene investigated herein is equally distributed in healthy individuals and patients with hepatitis C and does not seem to predict the response to therapy with interferon alfa-2a and ribavirin. Copyright (C) 2003 S. Karger AG, Basel
Quantitative Histomorphometry of the Healthy Peritoneum
The peritoneum plays an essential role in preventing abdominal frictions and
adhesions and can be utilized as a dialysis membrane. Its physiological
ultrastructure, however, has not yet been studied systematically. 106
standardized peritoneal and 69 omental specimens were obtained from 107
patients (0.1–60 years) undergoing surgery for disease not affecting the
peritoneum for automated quantitative histomorphometry and
immunohistochemistry. The mesothelial cell layer morphology and protein
expression pattern is similar across all age groups. Infants below one year
have a thinner submesothelium; inflammation, profibrotic activity and
mesothelial cell translocation is largely absent in all age groups. Peritoneal
blood capillaries, lymphatics and nerve fibers locate in three distinct
submesothelial layers. Blood vessel density and endothelial surface area
follow a U-shaped curve with highest values in infants below one year and
lowest values in children aged 7–12 years. Lymphatic vessel density is much
lower, and again highest in infants. Omental blood capillary density
correlates with parietal peritoneal findings, whereas only few lymphatic
vessels are present. The healthy peritoneum exhibits major thus far unknown
particularities, pertaining to functionally relevant structures, and subject
to substantial changes with age. The reference ranges established here provide
a framework for future histomorphometric analyses and peritoneal transport
modeling approaches
a global network of chronic kidney disease cohorts
Background Chronic kidney disease (CKD) is a global health burden, yet it is
still underrepresented within public health agendas in many countries. Studies
focusing on the natural history of CKD are challenging to design and conduct,
because of the long time-course of disease progression, a wide variation in
etiologies, and a large amount of clinical variability among individuals with
CKD. With the difference in health-related behaviors, healthcare delivery,
genetics, and environmental exposures, this variability is greater across
countries than within one locale and may not be captured effectively in a
single study. Methods Studies were invited to join the network. Prerequisites
for membership included: 1) observational designs with a priori hypotheses and
defined study objectives, patient-level information, prospective data
acquisition and collection of bio-samples, all focused on predialysis CKD
patients; 2) target sample sizes of 1,000 patients for adult cohorts and 300
for pediatric cohorts; and 3) minimum follow-up of three years. Participating
studies were surveyed regarding design, data, and biosample resources. Results
Twelve prospective cohort studies and two registries covering 21 countries
were included. Participants age ranges from >2 to >70 years at inclusion, CKD
severity ranges from stage 2 to stage 5. Patient data and biosamples (not
available in the registry studies) are measured yearly or biennially. Many
studies included multiple ethnicities; cohort size ranges from 400 to more
than 13,000 participants. Studies’ areas of emphasis all include but are not
limited to renal outcomes, such as progression to ESRD and death. Conclusions
iNET-CKD (International Network of CKD cohort studies) was established, to
promote collaborative research, foster exchange of expertise, and create
opportunities for research training. Participating studies have many
commonalities that will facilitate comparative research; however, we also
observed substantial differences. The diversity we observed across studies
within this network will be able to be leveraged to identify genetic,
behavioral, and health services factors associated with the course of CKD.
With an emerging infrastructure to facilitate interactions among the
investigators of iNET-CKD and a broadly defined research agenda, we are
confident that there will be great opportunity for productive collaborative
investigations involving cohorts of individuals with CKD
Low-dose Decitabine Vs best supportive care in older patients with AML and low blast counts: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC leukemia cooperative group and german MDS study group
Early Versus Late Allogeneic Hematopoietic Cell Transplantation in Patients with AML - Results From the Randomized AML 2003 Trial
HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation
The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these
loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant
pairs. There is preliminary evidence that these disparities may associate with increased
acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large
cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to
correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated
hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their
respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based nextgeneration
sequencing (NGS). All patients included received their first allogeneic
transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in
the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with
clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8%
(n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5
mismatches in the ARD associated with a worse overall survival (OS), as shown in
univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses
[hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLAmatched
subgroup. The worse outcome was mainly driven by a significantly higher nonrelapse
mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched
cases, the effect was not statistically significant. Our study results suggest that
mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome
of otherwise fully matched uHSCT and support their consideration upon donor selection in
the future
HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation
The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these
loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant
pairs. There is preliminary evidence that these disparities may associate with increased
acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large
cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to
correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated
hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their
respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based nextgeneration
sequencing (NGS). All patients included received their first allogeneic
transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in
the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with
clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8%
(n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5
mismatches in the ARD associated with a worse overall survival (OS), as shown in
univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses
[hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLAmatched
subgroup. The worse outcome was mainly driven by a significantly higher nonrelapse
mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched
cases, the effect was not statistically significant. Our study results suggest that
mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome
of otherwise fully matched uHSCT and support their consideration upon donor selection in
the future
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